Objective: Screen the pathogenic genes of a pedigree with clinical manifestation of familial dilated cardiomyopathy in Inner Mongolia. Methods: A total of 3 patients with dilated cardiomyopathy and 20 family members from the same family were examined in Ordos Central Hospital in Inner Mongolia from October, 2003 to August, 2017. Data on medical history, physical examinations, electrocardiograms, and echocardiography were obtained. 5 ml peripheral blood was sampled for per person. Chip Capture Sequencing technology was used to capture all the exons and splice sites of the genes that associated with hereditary cardiomyopathy and hereditary arrhythmia. The mutations in these genes were detected by high-throughput sequencing. All suspected pathogenic loci identified by high-throughput sequencing were verified by Sanger sequencing used for mutation detection. One hundred and fifty gender, age and race matched healthy people were included as the control group. Results: Pathogenic gene variations were detected in 3 symptomatic family members and 1 carrier from the pedigree. Five pathogenic gene variations were identified in the proband (Ⅱ1), a pSer236Gly and a pArg215Cys variation in the MYBPC3 gene, a pGln90Arg variation in the DSP gene, and pAsn2912Asp and pGlu2910Val variation in the DMD gene. One pathogenic variation was detected in Ⅲ3, which was a pArg215Cys variation in the MYBPC3 gene. Two pathogenic variations were detected in Ⅲ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. Two pathogenic variations were detected in the Ⅳ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. No gene variation loci were detected in the other family members and the control group. Conclusion: MYBPC3 gene, DSP gene and DMD gene variations are present in the familial dilated cardiomyopathy pedigree from Inner Mongolia, and these variations may be related with familial dilated cardiomyopathy.
目的： 通过对内蒙古自治区一家族性扩张型心肌病（DCM）家系进行致病基因筛查，探讨家族性DCM的致病基因突变位点。 方法： 入选2003年10月至2017年8月内蒙古鄂尔多斯市中心医院收治的同一家系的DCM患者3例及其家系成员20名。询问先证者及其家系成员的病史、家族史，并进行体格检查、常规心电图和超声心动图检查。同时每个家系成员抽取5 ml外周血，应用芯片捕获测序技术捕获遗传性心肌病及遗传性心律失常相关基因所有的外显子及剪切位点，通过高通量测序检测这些基因的突变情况，对高通量测序中出现的疑似致病位点，均通过突变检测的Sanger测序验证。另选取性别、年龄、种族与上述家系成员相匹配的健康人150名作为对照。 结果： 该家系中3例DCM患者和1例未发病者均检出相关的有害变异。先证者（女性）检出5个基因变异，分别为MYBPC3基因的p.Ser236Gly和p.Arg215Cys变异，DSP基因的p.Gln90Arg变异，DMD基因的p.Asn2912Asp和p.Glu2910Val变异。先证者二女儿检出1个基因变异，为MYBPC3基因的p.Arg215Cys变异。先证者三女儿检出2个基因变异，分别为MYBPC3基因的p.Ser236Gly变异和DSP基因的p.Gln90Arg变异。先证者外孙女检出2个基因变异，分别为MYBPC3基因的p.Ser236Gly变异和DSP基因的p.Gln90Arg变异。其余家系成员及健康对照人群均未检出上述基因变异位点。 结论： 该研究在内蒙古自治区一家族性DCM家系中发现MYBPC3、DSP、DMD基因的5个变异，而其可能与家族性DCM发病相关。.
Keywords: Cardiomyopathy, dilated; Genetic testing; Genetic variation.